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https://www.readbyqxmd.com/read/28542130/activation-of-transient-receptor-potential-vanilloid-4-involves-in-hypoxia-reoxygenation-injury-in-cardiomyocytes
#1
Qiong-Feng Wu, Cheng Qian, Ning Zhao, Qian Dong, Jing Li, Bin-Bin Wang, Lei Chen, Lixiu Yu, Bing Han, Yi-Mei Du, Yu-Hua Liao
Transient receptor potential vanilloid 4 (TRPV4) is highly expressed in heart and vessels and can be activated during myocardial ischemia/reperfusion (I/R). Recently, we found that treatment with a selective TRPV4 antagonist HC-067047 significantly reduced infarct size, decreased troponin T levels and improved cardiac function in murine model myocardial I/R. This study was undertaken to investigate the mechanism underlying TRPV4-mediated myocardial I/R injury. To mimic myocardial I/R injury, we established a hypoxia/reoxygenation (H/R) model in H9C2 cells and neonatal rat ventricle myocytes (NRVMs) in vitro...
May 25, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28536481/trpv4-dependent-induction-of-a-novel-mammalian-cold-inducible-protein-srsf5-as-well-as-cirp-and-rbm3
#2
Takanori Fujita, Hiroaki Higashitsuji, Hisako Higashitsuji, Yu Liu, Katsuhiko Itoh, Toshiharu Sakurai, Takahiro Kojima, Shuya Kandori, Hiroyuki Nishiyama, Motoi Fukumoto, Manabu Fukumoto, Koji Shibasaki, Jun Fujita
Cold-inducible RNA-binding protein (CIRP) and RNA-binding motif protein 3 (RBM3) are two evolutionarily conserved RNA-binding proteins that are structurally related to hnRNPs and upregulated in response to moderately low temperatures in mammalian cells. Although contributions of splicing efficiency, the gene promoters activated upon mild hypothermia and the transcription factor Sp1 to induction of CIRP have been reported, precise mechanisms by which hypothermia and other stresses induce the expression of mammalian cold-inducible proteins (CIPs) are poorly understood...
May 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28530703/trpv4-plays-a-role-in-breast-cancer-cell-migration-via-ca-2-dependent-activation-of-akt-and-downregulation-of-e-cadherin-cell-cortex-protein
#3
W H Lee, L Y Choong, T H Jin, N N Mon, S Chong, C S Liew, T Putti, S Y Lu, C Harteneck, Y P Lim
TRPV4 belongs to the 'Transient Receptor Potential' (TRP) superfamily. It has been identified to profoundly affect a variety of physiological processes, including nociception, heat sensation and inflammation. Unlike other TRP superfamily channels, its role in cancers are unknown until recently when we reported TRPV4 to be required for cancer cell softness that may promote breast cancer cell extravasation and metastasis. Here, we elucidated the molecular mechanisms mediated by TRPV4 in the metastatic breast cancer cells...
May 22, 2017: Oncogenesis
https://www.readbyqxmd.com/read/28528666/role-of-nonneuronal-trpv4-signaling-in-inflammatory-processes
#4
Pradeep Rajasekhar, Daniel P Poole, Nicholas A Veldhuis
Transient receptor potential (TRP) ion channels are important signaling components in nociceptive and inflammatory pathways. This is attributed to their ability to function as polymodal sensors of environmental stimuli (chemical and mechanical) and as effector molecules in receptor signaling pathways. TRP vanilloid 4 (TRPV4) is a nonselective cation channel that is activated by multiple endogenous stimuli including shear stress, membrane stretch, and arachidonic acid metabolites. TRPV4 contributes to many important physiological processes and dysregulation of its activity is associated with chronic conditions of metabolism, inflammation, peripheral neuropathies, musculoskeletal development, and cardiovascular regulation...
2017: Advances in Pharmacology
https://www.readbyqxmd.com/read/28526784/trpv4-mediates-the-calcium-influx-required-for-flightless-non-muscle-myosin-interaction-and-collagen-remodeling
#5
P D Arora, M Di Gregorio, P He, C A McCulloch
Collagen remodeling by phagocytosis requires cell extension formation, which in turn involves interaction of the actin binding protein Flightless I (FliI) with non-muscle myosin IIA (NMMIIA) at cell-matrix adhesion sites. As Ca(2+) plays a central role in controlling actomyosin-dependent functions, we examined how Ca(2+) controls the generation of cell extensions and collagen remodeling. Ratio fluorimetry demonstrated localized Ca(2+) influx at extensions of fibroblasts. Western Blotting and qPCR showed high expression levels of the Ca(2+)-permeable, Transient Receptor Potential Vanilloid-4 (TRPV4) channel, which co-immunoprecipitated with β1 integrin and localized to adhesions...
May 19, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28523109/discovery-of-gsk2193874-an-orally-active-potent-and-selective-blocker-of-transient-receptor-potential-vanilloid-4
#6
Mui Cheung, Weike Bao, David J Behm, Carl A Brooks, Michael J Bury, Sarah E Dowdell, Hilary S Eidam, Ryan M Fox, Krista B Goodman, Dennis A Holt, Dennis Lee, Theresa J Roethke, Robert N Willette, Xiaoping Xu, Guosen Ye, Kevin S Thorneloe
Transient Receptor Potential Vanilloid 4 (TRPV4) is a member of the Transient Receptor Potential (TRP) superfamily of cation channels. TRPV4 is expressed in the vascular endothelium in the lung and regulates the integrity of the alveolar septal barrier. Increased pulmonary vascular pressure evokes TRPV4-dependent pulmonary edema, and therefore, inhibition of TRPV4 represents a novel approach for the treatment of pulmonary edema associated with conditions such as congestive heart failure. Herein we report the discovery of an orally active, potent, and selective TRPV4 blocker, 3-(1,4'-bipiperidin-1'-ylmethyl)-7-bromo-N-(1-phenylcyclopropyl)-2-[3-(trifluoromethyl)phenyl]-4-quinolinecarboxamide (GSK2193874, 28) after addressing an unexpected off-target cardiovascular liability observed from in vivo studies...
May 11, 2017: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28523001/the-role-of-transient-receptor-potential-vanilloid-4-in-pulmonary-inflammatory-diseases
#7
REVIEW
Rachel G Scheraga, Brian D Southern, Lisa M Grove, Mitchell A Olman
Ion channels/pumps are essential regulators of organ homeostasis and disease. In the present review, we discuss the role of the mechanosensitive cation channel, transient receptor potential vanilloid 4 (TRPV4), in cytokine secretion and pulmonary inflammatory diseases such as asthma, cystic fibrosis (CF), and acute lung injury/acute respiratory distress syndrome (ARDS). TRPV4 has been shown to play a role in lung diseases associated with lung parenchymal stretch or stiffness. TRPV4 indirectly mediates hypotonicity-induced smooth muscle contraction and airway remodeling in asthma...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28512088/trpv4-in-the-battle-of-the-sexes
#8
Caitlin Sedwick
New JGP paper explains sexual dimorphism and tissue-specific activity of TRPV4.
May 16, 2017: Journal of General Physiology
https://www.readbyqxmd.com/read/28507079/distance-constraints-on-activation-of-trpv4-channels-by-akap150-bound-pkc%C3%AE-in-arterial-myocytes
#9
Sendoa Tajada, Claudia M Moreno, Samantha O'Dwyer, Sean Woods, Daisuke Sato, Manuel F Navedo, L Fernando Santana
TRPV4 (transient receptor potential vanilloid 4) channels are Ca(2+)-permeable channels that play a key role in regulating vascular tone. In arterial myocytes, opening of TRPV4 channels creates local increases in Ca(2+) influx, detectable optically as "TRPV4 sparklets." TRPV4 sparklet activity can be enhanced by the action of the vasoconstrictor angiotensin II (AngII). This modulation depends on the activation of subcellular signaling domains that comprise protein kinase C α (PKCα) bound to the anchoring protein AKAP150...
May 15, 2017: Journal of General Physiology
https://www.readbyqxmd.com/read/28501773/trpv4-functions-in-flow-shear-stress-induced-early-osteogenic-differentiation-of-human-bone-marrow-mesenchymal-stem-cells
#10
Kongzu Hu, Heyan Sun, Binjie Gui, Cong Sui
Mechanical cues have been shown to induce osteogenic differentiation of bone marrow stromal cells (MSCs). The TRPV4 channel, a Ca(2+)-permeable membrane ion channel, is implicated in the transduction of external mechanical stimulation into specific intracellular responses in a wide variety of bone cells. However, the role of TRPV4 in transducing and regulating the differentiation of human MSCs in response to flow shear stress (FSS) is unclear. In this study, using FSS and calcium imaging, we demonstrated that FSS activated early osteogenic differentiation, as shown by the early osteogenic differentiation marker osterix (Osx) and alkaline phosphatase (ALP) staining...
May 11, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28499580/transient-receptor-potential-trp-channels-as-molecular-targets-in-lung-toxicology-and-associated-diseases
#11
REVIEW
Alexander Dietrich, Dirk Steinritz, Thomas Gudermann
The lungs as the gateways of our body to the external environment are essential for gas exchange. They are also exposed to toxicants from two sides, the airways and the vasculature. Apart from naturally produced toxic agents, millions of human made chemicals were produced since the beginning of the industrial revolution whose toxicity still needs to be determined. While the knowledge about toxic substances is increasing only slowly, a paradigm shift regarding the proposed mechanisms of toxicity at the plasma membrane emerged...
April 26, 2017: Cell Calcium
https://www.readbyqxmd.com/read/28488242/marked-decrease-of-aquaporin-4-protein-is-independent-of-the-changes-in-%C3%AE-1-syntrophin-and-trpv4-levels-in-response-to-denervation-induced-muscle-atrophy-in-vivo
#12
Minenori Ishido, Tomohiro Nakamura
Aquaporin-4 (AQP4) is a selective water channel mediating water transport across cell membranes in skeletal muscles. Recently, it was noted that AQP4 is one of the key molecules regulating muscle morphology. Indeed, the AQP4 accumulation level was stably maintained in hypertrophied skeletal muscles. On the other hand, whether the AQP4 accumulation level is stably maintained in atrophied muscles remains poorly understood. The present study investigated the changes in the AQP4 accumulation level in the atrophied muscles at 2 weeks after denervation...
May 9, 2017: Journal of Muscle Research and Cell Motility
https://www.readbyqxmd.com/read/28473751/adropin-is-a-key-mediator-of-hypoxia-induced-anti-dipsogenic-effects-via-trpv4-camkk-ampk-signaling-in-the-circumventricular-organs-of-rats
#13
Fan Yang, Li Zhou, Xu Qian, Dong Wang, Wen-Juan He, Zhong-Wei Tang, Jun Yin, Qing-Yuan Huang
Water intake reduction (anti-dipsogenic effects) under hypoxia has been well established, but the underlying reason remains unknown. Our previous report indicated that activated TRPV4 neurons in SFO are associated with anti-dipsogenic effects under hypoxia. Although low partial pressure of blood oxygen directly activates TRPV4, humoral factors could also be involved. In the present study, we hypothesize that adropin, a new endogenous peptide hormone, was rapidly increased (serum and brain) concomitant with reduced water intake in early hypoxia...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28472069/detection-of-trpv4-channel-current-like-activity-in-fawn-hooded-hypertensive-fhh-rat-cerebral-arterial-muscle-cells
#14
Debebe Gebremedhin, David X Zhang, Dorothee Weihrauch, Nnamdi N Uche, David R Harder
The transient receptor potential vallinoid type 4 (TRPV4) is a calcium entry channel known to modulate vascular function by mediating endothelium-dependent vasodilation. The present study investigated if isolated cerebral arterial myocytes of the Fawn Hooded hypertensive (FHH) rat, known to display exaggerated KCa channel current activity and impaired myogenic tone, express TRPV4 channels at the transcript and protein level and exhibit TRPV4-like single-channel cationic current activity. Reverse transcription polymerase chain reaction (RT-PCR), Western blot, and immunostaining analysis detected the expression of mRNA transcript and translated protein of TRPV4 channel in FHH rat cerebral arterial myocytes...
2017: PloS One
https://www.readbyqxmd.com/read/28464448/gene-expression-changes-of-thermo-sensitive-transient-receptor-potential-channels-in-obese-mice
#15
Wuping Sun, Chen Lib, Yonghong Zhang, Changyu Jiang, Mingzhu Zhai, Qian Zhou, Lizu Xiao, Qiwen Deng
Adipose tissues play key roles in energy homeostasis. Brown adipocytes and beige adipocytes in white adipose tissue (WAT) sharethe similar characters of thermogenesis, both of them could be potential targets for obesity management. Several thermo-sensitive transient receptor potential channels (thermoTRPs) are shown to be involved in adipocyte biology. However, the expression pattern of thermoTRPs in adipose tissues from obese mice is still unknown. The mRNA expression of thermoTRPs in subcutaneous WAT (sWAT) and interscapular brown adipose tissue (iBAT) from lean and obese mice were measured using Reverse Transcriptase-quantitative PCRs (RT-qPCR)...
May 2, 2017: Cell Biology International
https://www.readbyqxmd.com/read/28459715/biphasic-renal-sympathetic-response-to-hemorrhagic-hypotension-in-mice
#16
Tao Zhang, Mamoru Tanida, Kunitoshi Uchida, Yoshiro Suzuki, Wei Yang, Yuhichi Kuda, Yasutaka Kurata, Makoto Tominaga, Toshishige Shibamoto
AIM: The inhibitory responses of renal sympathetic nerve activity (RSNA) and heart rate (HR) to sustained hemorrhagic shock occurred in anesthetized rats, but have not yet been determined in mice. Here, we investigated the responses of RSNA and HR to hemorrhagic hypotension in anesthetized mice, with an emphasis on the molecule-based mechanism for roles of afferent vagal nerves. METHODS: RSNA, HR, and mean systemic arterial pressure (MAP) were continuously measured in male pentobarbital-anesthetized C57BL/6N mice...
April 28, 2017: Shock
https://www.readbyqxmd.com/read/28456852/fluid-induced-lung-injury-role-of-trpv4-channels
#17
Shailesh Bihari, Dani-Louise Dixon, Mark D Lawrence, Dylan De Bellis, Claudine S Bonder, David P Dimasi, Andrew D Bersten
Administration of bolus intravenous fluid is associated with respiratory dysfunction and increased mortality, findings with no clear mechanistic explanation. The objective of this study was to examine whether bolus intravenous (i.v.) fluid administration results in acute lung injury in a rat model and further, to examine whether this injury is associated with transient receptor potential vallinoid (TRPV)4 channel function and endothelial inflammatory response. Healthy male Sprague-Dawley rats were administered 60 ml/kg 0...
April 29, 2017: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/28456383/adult-onset-spinal-muscular-atrophy-an-update
#18
REVIEW
R Juntas Morales, N Pageot, G Taieb, W Camu
Spinal muscular atrophy (SMA) refers to a group of disorders affecting lower motor neurons. The age of onset of these disorders is variable, ranging from the neonatal period to adulthood. Over the last few years, there has been enormous progress in the description of new genes and phenotypes that throw new light on the molecular pathways involved in motor neuron degeneration. Advances in our understanding of the pathophysiology of the most frequent forms, SMA linked to SMN1 gene mutations and Kennedy disease, has led to the development of therapeutic strategies currently being tested in clinical trials...
April 26, 2017: Revue Neurologique
https://www.readbyqxmd.com/read/28438566/t-type-voltage-gated-calcium-channels-are-involved-in-endothelium-dependent-relaxation-of-mice-pulmonary-artery
#19
Guillaume Gilbert, Arnaud Courtois, Mathilde Dubois, Laure-Anne Cussac, Thomas Ducret, Philippe Lory, Roger Marthan, Jean-Pierre Savineau, Jean-François Quignard
In pulmonary arterial endothelial cells, Ca(2+) channels and intracellular Ca(2+)concentration ([Ca(2+)]i) control the release of vasorelaxant factors such as nitric oxide and are involved in the regulation of pulmonary arterial blood pressure. The present study was undertaken to investigate the implication of T-type voltage-gated Ca(2+)channels (T-VGCCs, Cav3.1 channel) in the endothelium-dependent relaxation of intrapulmonary arteries. Relaxation was quantified by means of a myograph in wild type and Cav3...
April 21, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28433656/impaired-endothelium-derived-hyperpolarization-type-relaxation-in-superior-mesenteric-arteries-isolated-from-female-otsuka-long-evans-tokushima-fatty-rats
#20
Takayuki Matsumoto, Shota Kobayashi, Makoto Ando, Shun Watanabe, Maika Iguchi, Kumiko Taguchi, Tsuneo Kobayashi
Endothelium-derived hyperpolarization (EDH) is an important signaling mechanism of endothelium-dependent vasorelaxation, and little attention has been paid to the EDH-type responses in female metabolic syndrome such as that observed with type-2 diabetes. We previously reported that EDH-type relaxation was impaired in superior mesenteric arteries from male Otsuka Long-Evans Tokushima Fatty (OLETF) rat, a model of type-2 diabetes, however, the response was unclear in female OLETF rat. Thus, the aim of this study was to examine if EDH-type relaxation was altered in superior mesenteric arteries isolated from female OLETF rats compared to age-matched, control female Long-Evans Tokushima Otsuka (LETO) rats at age 50-59 weeks...
April 19, 2017: European Journal of Pharmacology
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